Abstract
Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Recent advances in the understanding of the biology of tumors and in highly sensitive detection technologies for molecular analysis offer targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. However, our understanding of an individual patient’s lung cancer is often limited by tumor accessibility because of the high risk and invasive nature of current tissue biopsy procedures. “Liquid biopsy”, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), offers a new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to more personalized treatment. In this review, we examined the clinical significance and uniqueness of CTCs and ctDNA from NSCLC patients, isolation and detection methods developed to analyze each type of circulating biomarker, and examples of clinical studies of potential applications for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to therapy. We also discuss challenges that remain to be addressed before such tools are implemented for routine use in clinical settings.
Highlights
Lung cancer is the most common cause of cancer-related mortality in both men and women worldwide, with 1.8 million new cases reported every year [1,2]
We present a brief overview of clinical perspectives concerning and opportunities for the use of liquid biopsy in lung cancer, focusing on the following: identification of actionable mutations, such as sensitizing (19 del and L858R) and resistant (T790M) epidermal growth factor receptor (EGFR) mutations; the significance and uniqueness of the two most popular circulating biomarkers, i.e., circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA); and the detection methods for each biomarker and the current limitations of these methods
This study demonstrated the analysis of the cobas® EGFR Mutation Test v2, which is a PCR-based assay that has been developed for the detection of EGFR mutations, including a T790M mutation, for treatment with osimertinib, which was approved by the Food and Drug Administration (FDA) in 2016 [54]
Summary
Lung cancer is the most common cause of cancer-related mortality in both men and women worldwide, with 1.8 million new cases reported every year [1,2]. Recent advances in our understanding of molecular abnormalities in lung cancer and in highly sensitive molecular analysis technologies have revealed that targeted therapies such as the use of EGFR tyrosine kinase inhibitor (TKI) drugs can deliver improved clinical outcomes for certain groups of patients with advanced NSCLC [3,4,5,6,7]. We present a brief overview of clinical perspectives concerning and opportunities for the use of liquid biopsy in lung cancer, focusing on the following: identification of actionable mutations, such as sensitizing (19 del and L858R) and resistant (T790M) EGFR mutations; the significance and uniqueness of the two most popular circulating biomarkers, i.e., CTCs and ctDNA; and the detection methods for each biomarker and the current limitations of these methods. We discuss the key areas of potential clinical applications of liquid biopsy using CTCs and ctDNA in early diagnosis, prognosis, and monitoring of response and resistance to treatment, as well as obstacles that remain to be overcome before liquid biopsy is implemented routinely in clinical settings
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